Abstract
Monocular deprivation early in development leads to anatomical and physiological changes in visual cortex that result in poor visual acuity in the deprived eye. Behavioural studies have shown that binocular visual experience is necessary for optimal recovery, however, the mechanisms that promote this recovery are not well understood. Multiple mechanisms mediate plasticity in developing visual cortex including excitatory (NMDA, AMPA) and inhibitory (GABAA) receptors. To address this question, we initiated a comprehensive study of changes in excitatory and inhibitory plasticity in visual cortex of cats reared with either normal vision, monocular deprivation, or monocular deprivation followed by a brief period of binocular vision. Using Western blot analysis of samples from different regions of visual cortex, we examined changes in excitatory (NR1, NR2A, NR2B, GluR2) and inhibitory (GABAAa1, GABAAa3) receptor subunit expression. Monocular deprivation promoted a complex pattern of changes that were most severe in regions of visual cortex where the central visual field is represented. To analyze these changes, we applied a neuroinormatics approach using Principle Component Analysis (PCA) to characterize the global pattern of change in these plasticity mechanisms. PCA showed that monocular deprivation causes a significant shift of the developmental trajectory, bypassing a large proportion of the normal developmental path, and accelerates maturation of the global receptor subunit expression. These changes suggest that monocularly deprived animals have less developmental plasticity and lack the molecular machinery needed for functional maturation of cortical circuits. A brief 4 day period of binocular vision was sufficient to restore these important plasticity mechanisms towards that of normal animals. Together, these results provide insights into molecular mechanisms underlying amblyopia, and why binocular vision is crucial for optimal recovery.